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https://www.readbyqxmd.com/read/28339196/discovery-of-a-small-molecule-degrader-of-bromodomain-and-extra-terminal-bet-proteins-with-picomolar-cellular-potencies-and-capable-of-achieving-tumor-regression
#1
Bing Zhou, Jiantao Hu, Fuming Xu, Zhuo Chen, Longchuan Bai, Ester Fernandez-Salas, Mei Lin, Liu Liu, Chao-Yie Yang, Yujun Zhao, Donna McEachern, Sally Przybranowski, Bo Wen, Duxin Sun, Shaomeng Wang
The bromodomain and extra-terminal (BET) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT members, are epigenetic "readers" and play a key role in the regulation of gene transcription. BET proteins are considered to be attractive therapeutic targets for cancer and other human diseases. Recently, heterobifunctional small-molecule BET degraders have been designed based upon the proteolysis targeting chimera (PROTAC) concept to induce BET protein degradation. Herein, we present our design, synthesis, and evaluation of a new class of PROTAC BET degraders...
March 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28336744/association-of-respiratory-symptoms-and-asthma-with-occupational-exposures-findings-from-a-population-based-cross-sectional-survey-in-telemark-norway
#2
R Abrahamsen, A K M Fell, M V Svendsen, E Andersson, K Torén, P K Henneberger, J Kongerud
OBJECTIVES: The aim of this study was to estimate the prevalence of respiratory symptoms and physician-diagnosed asthma and assess the impact of current occupational exposure. DESIGN: Cross-sectional analyses of the prevalence of self-reported respiratory health and association with current occupational exposure in a random sample of the general population in Telemark County, Norway. SETTINGS: In 2013, a self-administered questionnaire was mailed to a random sample of the general population, aged 16-50, in Telemark, Norway...
March 22, 2017: BMJ Open
https://www.readbyqxmd.com/read/28322799/novel-method-for-measurement-of-heparin-anticoagulant-activity-using-spr
#3
Jing Zhao, Xinyue Liu, Anju Malhotra, Quanhong Li, Fuming Zhang, Robert J Linhardt
A novel method has been developed for the easy measurement of heparin's anticoagulant activity using surface plasmon resonance. The anticoagulant activity of target heparin was evaluated by measuring the competitive antithrombin III binding of analyte heparin in the solution phase and USP heparin immobilized on chip surface. Heparins, obtained from different animal sources, and low molecular weight heparins were analyzed. The results were reproducible and correlated well with the results of chromogenic assays (correlation coefficient r = 0...
March 18, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28297651/glycan-determinants-of-heparin-tau-interaction
#4
Jing Zhao, Isabelle Huvent, Guy Lippens, David Eliezer, Anqiang Zhang, Quanhong Li, Peter Tessier, Robert J Linhardt, Fuming Zhang, Chunyu Wang
Tau aggregates into paired helical filaments within neurons, a pathological hallmark of Alzheimer's disease. Heparin promotes tau aggregation and recently has been shown to be involved in the cellular uptake of tau aggregates. Although the tau-heparin interaction has been extensively studied, little is known about the glycan determinants of this interaction. Here, we used surface plasmon resonance (SPR) and NMR spectroscopy to characterize the interaction between two tau fragments, K18 and K19, and several polysaccharides, including heparin, heparin oligosaccharides, chemically modified heparin, and related glycans...
March 14, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28296532/allergic-diseases-smoking-and-environmental-exposure-among-university-students-in-lebanon
#5
Souheil Hallit, Tarek Bou Assy, Rabih Hallit, Pascale Salameh
INTRODUCTION: Smoking habits among university students in Lebanon are not clearly identified, and studies correlating these habits to asthma and allergic diseases are lacking. The primary objective of this study is to assess the asthma and allergic diseases' predictors, particularly cigarette and/or waterpipe smoking and other environmental exposures, among university students. A second objective is to evaluate the potential role of these predictors as correlates of health-related self-assessment...
March 15, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28294264/iron-cobalt-bimetal-oxide-nanorods-as-efficient-and-robust-water-oxidation-catalysts
#6
Xichen Zhou, Jingwei Huang, Fuming Zhang, Yukun Zhao, Yan Zhang, Yong Ding
Cobalt-based oxides are considered as potential water oxidation catalysts for future artificial photosynthetic systems because of their high abundance, strong stability and efficient performance. Herein, a series of cobalt-based oxides, MnCo3-nO4 (M = Mn, Fe, Co) samples, were synthesized through changing the metal sources by a low-temperature coprecipitation method. These catalysts were investigated under photochemical and electrochemical water oxidation conditions. And they all exhibited efficient activity for water oxidation under alkaline, acidic and neutral conditions under visible light irradiation...
March 15, 2017: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/28289365/br%C3%A3-lologie-et-m%C3%A3-decine-l%C3%A3-gale-les-victimes-d%C3%A2-incendie
#7
R Costagliola, J-P Campana, M Costagliola
During a judicial inquiry, the forensic doctor is frequently required to examine the hospitalized fire victim. He has to produce a certificate on the burns, defining their origin, seriousness and prognosis. The expert assessment of serious burn victims consists in an overall evaluation of functional and psychological sequelae, and can be conducted only after the long period of treatment needed for them to heal. The expert must know the forensic rules concerning the specific features of sequelae that follow a cutaneous burn injury...
December 31, 2016: Annals of Burns and Fire Disasters
https://www.readbyqxmd.com/read/28285017/effects-of-the-aryl-hydrocarbon-receptor-agonist-3-methylcholanthrene-on-the-17%C3%AE-estradiol-regulated-mrna-transcriptome-of-the-rat-uterus
#8
Janina Helle, Annekathrin M Keiler, Oliver Zierau, Peggy Dörfelt, Günter Vollmer, Leane Lehmann, Sridar V Chittur, Martin Tenniswood, JoEllen Welsh, Georg Kretzschmar
Polycyclic aromatic hydrocarbons (PAHs) are products of incomplete combustion of organic compounds, abundant in exhaust fumes and cigarette smoke. They act by binding to the aryl hydrocarbon receptor (AHR) which induces expression of phase 1 and phase 2 enzymes in the liver. PAH induced AHR activation may also lead to adverse effects by modulating other pathways, for example estrogen receptor (ER) signaling in the female reproductive tract. We have investigated the effects of the PAH 3-methylcholanthrene (3-MC) on 17β-estradiol (E2) dependent signaling in the uterus of ovariectomized rats to characterize the cross talk between AHR and ER on an mRNA transcriptome wide scale...
March 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28282892/detection-of-the-vibration-signal-from-human-vocal-folds-using-a-94-ghz-millimeter-wave-radar
#9
Fuming Chen, Sheng Li, Yang Zhang, Jianqi Wang
The detection of the vibration signal from human vocal folds provides essential information for studying human phonation and diagnosing voice disorders. Doppler radar technology has enabled the noncontact measurement of the human-vocal-fold vibration. However, existing systems must be placed in close proximity to the human throat and detailed information may be lost because of the low operating frequency. In this paper, a long-distance detection method, involving the use of a 94-GHz millimeter-wave radar sensor, is proposed for detecting the vibration signals from human vocal folds...
March 8, 2017: Sensors
https://www.readbyqxmd.com/read/28278175/pneumococcal-infection-of-respiratory-cells-exposed-to-welding-fumes-role-of-oxidative-stress-and-hif-1-alpha
#10
Jonathan Grigg, Lisa Miyashita, Reetika Suri
Welders are more susceptible to pneumococcal pneumonia. The mechanisms are yet unclear. Pneumococci co-opt the platelet activating factor receptor (PAFR) to infect respiratory epithelial cells. We previously reported that exposure of respiratory cells to welding fumes (WF), upregulates PAFR-dependent pneumococcal infection. The signaling pathway for this response is unknown, however, in intestinal cells, hypoxia-inducible factor-1 α (HIF 1α) is reported to mediate PAFR-dependent infection. We sought to assess whether oxidative stress plays a role in susceptibility to pneumococcal infection via the platelet activating factor receptor...
2017: PloS One
https://www.readbyqxmd.com/read/28274239/occupational-exposure-to-particles-and-mitochondrial-dna-relevance-for-blood-pressure
#11
Yiyi Xu, Huiqi Li, Maria Hedmer, Mohammad Bakhtiar Hossain, Håkan Tinnerberg, Karin Broberg, Maria Albin
BACKGROUND: Particle exposure is a risk factor for cardiovascular diseases. Mitochondrial DNA (mtDNA) is a primary target for oxidative stress generated by particle exposure. We aimed to elucidate the effects of occupational exposure to particle-containing welding fumes on different biomarkers of mtDNA function, and in turn, explore if they modify the association between particle exposure and cardiovascular response, measured as blood pressure. METHODS: We investigated 101 welders and 127 controls (all non-smoking males) from southern Sweden...
March 9, 2017: Environmental Health: a Global Access Science Source
https://www.readbyqxmd.com/read/28272399/maternal-and-paternal-occupational-exposures-and-hepatoblastoma-results-from-the-hope-study-through-the-children-s-oncology-group
#12
Amanda E Janitz, Gurumurthy Ramachandran, Gail E Tomlinson, Mark Krailo, Michaela Richardson, Logan Spector
Little is known about the etiology of hepatoblastoma. We aimed to confirm the results of a previous study evaluating the association between parental occupational exposures and hepatoblastoma. In our case-control study, we identified cases (n=383) from the Children's Oncology Group and controls from birth certificates (n=387), which were frequency matched to cases on year and region of birth, sex, and birth weight. Occupational exposure in the year before and during the index pregnancy was collected through maternal interview and analyzed using unconditional logistic regression...
March 8, 2017: Journal of Exposure Science & Environmental Epidemiology
https://www.readbyqxmd.com/read/28267513/isolation-of-a-lectin-binding-rhamnogalacturonan-i-containing-pectic-polysaccharide-from-pumpkin
#13
Jing Zhao, Fuming Zhang, Xinyue Liu, Kalib St Ange, Anqiang Zhang, Quanhong Li, Robert J Linhardt
A rhamnogalacturonan-I (RG-I) containing pectic polysaccharide (PPc) was isolated from pumpkin following a low-temperature alkali treatment and a combination of gradual alcohol precipitation and ion-exchange. Monosaccharide compositional analysis of PPc revealed the presence of rhamnose, galacturonic acid, galactose, and arabinose in a molar ratio of 7.4: 25: 28: 2.6. Structural and linkage analysis by 1D NMR ((1)H NMR and (13)C NMR), and 2D NMR (COSY, TOCSY, HSQC, and elevated temperature HMBC) suggested that PPc was a RG-I-like pectic polysaccharide, branched at the C-4 of some of the (about 29% of) rhamnosyl units, with relatively long β-1,4-d-galactan side chains to which were attached, through the C-3 of β-d-Gal, terminal non reducing α-Araf units...
May 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28264671/lifestyles-and-socio-cultural-factors-among-children-aged-6-8-years-from-five-italian-towns-the-mapec_life-study-cohort
#14
Francesco Bagordo, Antonella De Donno, Tiziana Grassi, Marcello Guido, Gabriele Devoti, Elisabetta Ceretti, Claudia Zani, Donatella Feretti, Milena Villarini, Massimo Moretti, Tania Salvatori, Annalaura Carducci, Marco Verani, Beatrice Casini, Sara Bonetta, Elisabetta Carraro, Tiziana Schilirò, Silvia Bonizzoni, Alberto Bonetti, Umberto Gelatti
BACKGROUND: Lifestyles profoundly determine the quality of an individual's health and life since his childhood. Many diseases in adulthood are avoidable if health-risk behaviors are identified and improved at an early stage of life. The aim of the present research was to characterize a cohort of children aged 6-8 years selected in order to perform an epidemiological molecular study (the MAPEC_LIFE study), investigate lifestyles of the children that could have effect on their health status, and assess possible association between lifestyles and socio-cultural factors...
March 7, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28264409/notes-on-the-genus-i-larnaca-i-walker-1869-orthoptera-gryllacridinae-from-china
#15
Baojie DU, Xun Bian, Fuming Shi
Walker (1869) proposed the genus Larnaca with type species Larnaca fasciata Walker, 1869. Karny (1937) gave the characters of the genus and listed 8 species. Gorochov (2003) subdivided the genus into two subgenera: Larnaca and Paralarnaca, and their type species are Larnaca (Larnaca) fasciata Walker, 1869 (Malesia) and Larnaca (Paralarnaca) johni (Griffini, 1911) (Malesia) respectively, and described 2 new species, i.e. Larnaca (Larnaca) vietnamensis Gorochov, 2003 (type locality: Vietnam) and Larnaca (Larnaca) phetchaburi Gorochov, 2003 (type locality: Thailand)...
February 13, 2017: Zootaxa
https://www.readbyqxmd.com/read/28260879/occupational-copd-and-job-exposure-matrices-a-systematic-review-and-meta-analysis
#16
REVIEW
Steven Sadhra, Om P Kurmi, Sandeep S Sadhra, Kin Bong Hubert Lam, Jon G Ayres
BACKGROUND: The association between occupational exposure and COPD reported previously has mostly been derived from studies relying on self-reported exposure to vapors, gases, dust, or fumes (VGDF), which could be subjective and prone to biases. The aim of this study was to assess the strength of association between exposure and COPD from studies that derived exposure by job exposure matrices (JEMs). METHODS: A systematic search of JEM-based occupational COPD studies published between 1980 and 2015 was conducted in PubMed and EMBASE, followed by meta-analysis...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28258373/acute-respiratory-effects-and-biomarkers-of-inflammation-due-to-welding-derived-nanoparticle-aggregates
#17
Katrin Dierschke, Christina Isaxon, Ulla B K Andersson, Eva Assarsson, Anna Axmon, Leo Stockfelt, Anders Gudmundsson, Bo A G Jönsson, Monica Kåredal, Jakob Löndahl, Joakim Pagels, Aneta Wierzbicka, Mats Bohgard, Jörn Nielsen
PURPOSE: Welders are exposed to airborne particles from the welding environment and often develop symptoms work-related from the airways. A large fraction of the particles from welding are in the nano-size range. In this study we investigate if the welders' airways are affected by exposure to particles derived from gas metal arc welding in mild steel in levels corresponding to a normal welding day. METHOD: In an exposure chamber, 11 welders with and 10 welders without work-related symptoms from the lower airways and 11 non-welders without symptoms, were exposed to welding fumes (1 mg/m(3)) and to filtered air, respectively, in a double-blind manner...
March 3, 2017: International Archives of Occupational and Environmental Health
https://www.readbyqxmd.com/read/28255757/occupational-risk-factors-for-nasopharyngeal-carcinoma-in-hong-kong-chinese-a-case-referent-study
#18
Shao-Hua Xie, Ignatius Tak-Sun Yu, Lap Ah Tse, Joseph Siu Kie Au, June Sze Man Lau
PURPOSE: This study aimed to investigate the occupational risk factors for nasopharyngeal carcinoma (NPC) in Hong Kong Chinese. METHODS: We conducted a case-referent study with 352 incident cases and 410 referents recruited between June 2010 and December 2012. Full occupational histories were obtained via face-to-face interviews. Unconditional logistic regressions were performed to estimate the odds ratios (ORs) for NPC associated with occupational risk factors...
March 2, 2017: International Archives of Occupational and Environmental Health
https://www.readbyqxmd.com/read/28251527/oxidative-stress-and-early-dna-damage-in-workers-exposed-to-iron-rich-metal-fumes
#19
Masoud Pandeh, Saedeh Fathi, Mohammad Javad Zare Sakhvidi, Javad Zavar Reza, Lyla Sedghian
Occupational exposure to metal fumes occurs routinely in many occupational settings. The inflammatory response to fumes and metals after exposure could lead to an increase in reactive oxygen species and level of DNA damage. In this study, the level of early DNA damage and oxidative stress was evaluated in a group of steel company (n = 30) and compared to the non-exposed (n = 28) subjects. All DNA damage markers in workers were significantly higher in exposed group in comparison with controls (p < 0...
March 1, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28238800/activation-of-the-cold-receptor-trpm8-by-low-levels-of-menthol-in-tobacco-products
#20
Meike Paschke, Anna Tkachenko, Katja Ackermann, Christoph Hutzler, Frank Henkler, Andreas Luch
Activation of the cold-receptor TRPM8 by menthol or other tobacco additives can suppress natural defense reactions such as coughing that usually would become effective as involuntary resistance against the inhalation of fumes. In Europe menthol is only regulated as flavor, but can be used as additive as long as no characteristic mint-like aroma will become noticeable in the end-product tobacco. The question needs to be addressed of whether such comparatively minor contents would be sufficient to trigger a measurable activation of TRPM8...
February 24, 2017: Toxicology Letters
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